Ensemble-Based Docking on GPCRs: Toward Toxicity Prediction

Ensemble-Based Docking on GPCRs: Toward Toxicity Prediction


  • Wilfredo Evangelista Falcon, The University of Tennessee, Knoxville
October 23, 2017 - 11:00am to 12:00pm


Nowadays, docking techniques are not only used to study potential targets, but also to analyze the interaction with possible off-target receptors. The latest has been facilitated by completion of the Human Genome Project, which has uncovered many targetable and off-targetable receptors. Consequently, the goal of predicting adverse drug reactions for novel drug candidates has become a realistic objective. In this work, we present the basis of a reliable framework for high-throughput ensemble-based docking that allows protein-drug interaction predictions with an unbiased statistical significance and consequently prevents false positive and/or negative hits, making it possible to select conformations with better binding performance than the random selection distribution. Crystal structures and representative conformations of clustered trajectories for eight G protein-coupled receptors were examined. Then, four of those proteins were the subjects of a subsequent screening on each conformational state of their respective trajectories. The experiment showed that the high-throughput screening technique is better than the crystal-structure or random-selection approaches. It is much more efficient when it is performed on each frame of the molecular dynamics trajectory.

Additional Information 

Please contact Lora Davis (574-6308, davislb@ornl.gov) for building access.

Sponsoring Organization 

Center for Molecular Biophysics


  • Building: 2040
  • Room: Third-Floor Classroom

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